Receptor tyrosine kinase stimulates cell-matrix adhesion by phosphatidylinositol 3 kinase and phospholipase C-gamma 1 pathways

Receptor tyrosine kinases are known to be important in growth and differentiation. We have recently found that c-kit, the tyrosine kinase receptor for steel factor, also regulates cell-matrix adhesion. Because Steel factor helps regulate cell migration and localization, this may be an important biologic function. Integrin adhesiveness is regulated within minutes by c-kit. The signaling pathways for tyrosine kinase stimulation of integrin adhesiveness and their relation to pathways that regulate growth and differentiation over much longer time periods remain uncharacterized. We have studied the effector pathways by which receptor tyrosine kinases regulate cell-matrix adhesion using wild-type and mutant forms of the platelet-derived growth factor (PDGF) receptor, which is closely related to c-kit. The PDGF receptor expressed in mast cells is as potent as c-kit in stimulating adhesion to fibronectin. We show that induction of adhesion is regulated through two independent pathways of phosphatidylinositol 3 kinase (PI3K) and phospholipase C- gamma 1 (PLC gamma)-protein kinase C by elimination of autophosphorylation sites required for activation of PI3K and PLC gamma or in combination with downregulation of protein kinase C or wortmannin. By contrast, a receptor mutated in both the PI3K and PLC gamma association sites can still stimulate mast cell growth, indicating a crucial role of these effector molecules in regulating adhesion rather than cell growth.     

Acute normovolemic hemodilution is a cost-effective alternative to preoperative autologous blood donation by patients undergoing radical retropubic prostatectomy

BACKGROUND: Preoperative autologous blood donation is accepted as a standard of care for radical prostatectomy. Acute normovolemic hemodilution (ANH) is an alternative method for obtaining autologous blood. The cost and benefits of these two autologous blood-collection techniques are compared. STUDY DESIGN AND METHODS: Thirty consecutive patients scheduled for radical prostatectomy underwent ANH to a target hematocrit level of 28 percent. Blood was transfused in the perioperative period to maintain the hematocrit level > 25 percent. Hematocrit levels, transfusion outcomes and costs, and postoperative outcomes for these patients (hemodilution group) were compared with a matched patient cohort who preoperatively donated 3 units of blood for autologous use in prostatectomy surgery (nonhemodilution group, n = 30). RESULTS: Thirty patients underwent ANH to a hematocrit level of 28.7 +/− 1.7 percent, and 1740 +/− 346 mL (3.5 +/− 0.7 units) of blood were collected. Three (10%) of the patients in each cohort had allogeneic blood exposure. Transfusion costs were 73 percent higher for the nonhemodilution group patients than for the hemodilution group patients ($330 +/− $100 vs. $191 +/− $55, p < 0.001). No differences were found in postoperative outcomes. CONCLUSION: An integrated blood conservation program utilizing hemodilution and a defined transfusion trigger can decrease the requirement for preoperative donation of blood for autologous use in radical prostatectomy. Point-of-care autologous blood procurement is more cost-effective than preadmission donation of autologous blood units.     

PHYSICAL HEALTH OF TEN-YEAR-OLD CHILDREN An Epidemiological Study of School Children and a Follow-up of Previous Health Care

ABSTRACT. At 10 years of age, all 223 children in a school district underwent a physical examination and a screening for vision and hearing defects within the school health services. The purpose of the study was to detect health problems of importance for the day-to-day functioning of the child. In 26.1% significant deviations were found. Physical disorders comprised 11.7%, visual defects 11.7% and auditory impairment 2.7%. The vast majority of significant health problems were previously known and in only 4.4% of the 223 children newly detected, 0.9% by the physical examination, 2.7% by the vision screening and 0.9% by the auditory screening. The most frequent health problem of all was allergy in 13.5%, in 5.4% regarded as functionally important. Minor orthopaedic deviations and motor disturbances were common but not often considered to affect the functioning of the child significantly. As a whole, the children's health was very good and the outcome of the physical examination at this age was not impressive. It is evident that the physician's role in the school health system needs to be reconsidered.     

CHYMOTRYPTIC ACTIVITY IN STOOL OF LOW BIRTH WEIGHT INFANTS IN THE FIRST WEEK OF LIFE

ABSTRACT: Jodl, J., Kornfalt, R. and Svenningsen, N. YV. (The Motol Paediatric Clinic, University of Prague, Prague, Czechoslovakia, and the Department of Paediatrics, University Hospital, Lund, Sweden). Chymotryptic activity in stool of low birth weight infants in the first week of life. Acta Paediatr Scand, 64:619, 1975.–Pancreatic enzyme activity in low birth weight (LBW) infants during the first postnatal week has been evaluated by analysing the chymotrypsin content of 198 stool specimens from 42 LBW infants with birth weights ranging between 750 and 2570 g. A wide variation in chymotryptic activity yet with a tendency to initially low values with a peak on the third day after birth was found. Small-for-gestational age (SGA) infants had significantly lower values than appropriate-for-gestational age (AGA) infants. This is considered due to intra-uterine malnutrition with secondary pancreatic dysfunction in SGA infants. In screening program for cystic fibrosis or other defects of exocrine pancreatic activity, low stool chymotrypsin values cannot be considered pathological until after the fourth day of life.     

Acute Respiratory Tract Infections in Children

ABSTRACT. Respiratory tract infections (RTIs) in small children account for a considerable proportion of health care expenditure. In 113 children, followed for the first three years of life, we studied the frequency of acute RTI and its relationship to the factors: type of day-care, age, sex, family size, living conditions, allergic predisposition, family smoking habits, and season. To elucidate the influence of age, the frequency of acute RTI and its relationship to type of day-care was longitudinally studied on a quarterly basis. The frequency of acute RTI diagnosis increased gradually from birth culminating in a peak at the beginning of the second year. Besides age and season, type of day-care was the only factor studied to show any relationship with the frequency of acute RTI diagnosis. Up to the age of almost 2 1/2 years, children attending day-care centres accounted for more RTI diagnoses than did those in home care or family day-care, categories with comparable frequncies.     

Electron microscopy study of genesis and dynamics of immunodeposition in IgMk-IgG cryoglobulin-induced glomerulonephritis in mice

Cryoglobulinemic glomerulonephritis is particularly frequent in type II mixed IgMk-IgG cryoglobulinemia. The typical form is a membranoproliferative glomerulonephritis with a particular monocyte infiltration. In the most severe cases, there is occlusion of the capillary lumina by the same immunoglobulin constituents of the cryoprecipitate. While it is generally accepted that the "hyaline thrombi" are endoluminal aggregates of IgG-IgM immune complexes, probably favored by high endocapillary concentration of cryoglobulins, the modality of generation has not been studied. To study the dynamic formation of such "thrombi," we reproduced an experimental model of cryoglobulinemic glomerulonephritis in mice by injecting them twice a day for 3 days with 4 mg human IgMk-IgG cryoglobulins previously solubilized at 37 degrees C. The dynamic formation of immunodeposits was studied by immunofluorescence and electron microscopy. After 1 day, only mesangial deposits were found; after 3 days, in addition to mesangial deposition, all the capillary lumina were occluded by huge electron-dense bodies. To look for and quantify the contacts between such "thrombi" and mesangial or subendothelial deposits, we obtained serial, ultrathin, 0.5-microm sections that allowed us to reconstruct the whole glomerular tuft. Within each serial section, there was continuity between hyaline thrombi and mesangial or subendothelial deposits ranging from 80% to 85% of the capillary loops. The percentage was 100% for two adjacent serial sections. In conclusion, our data demonstrate directly for the first time that hyaline thrombi follow mesangial deposits. The high percentage of contacts between thrombi and mesangial or subendothelial deposits suggests that they result from in situ build-up of true huge endoluminal immunodeposits after saturation of the clearance capacity of the mesangium.     

Computed tomography and magnetic resonance imaging evaluation of patellofemoral instability

Malalignment and tracking abnormalities of the patellofemoral joint are common causes of anterior knee pain,which are often difficult to evaluate clinically. Conventional radiography, as well as the cross-sectional imaging modalities of computed tomography (CT) and magnetic resonance imaging (MRI) are useful tools for both detecting and quantifying these abnormalities. Acute transient dislocation of the patella, on the other hand, is a relatively uncommon injury accounting for only 2% to 3% of all acute injuries of the knee, and can also be a difficult diagnosis to establish on the basis of history and physical findings alone. MRI is a sensitive, noninvasive method for detecting prior acute transient dislocation of the patella. This article begins by describing the role of CT and MRI as it pertains to the detection of abnormal patellofemoral tracking. Both static and dynamic techniques are described along with the standard criteria used to establish and quantify patellofemoral malalignment abnormalities. Next, the constellation of MRI findings most commonly encountered after acute transient dislocation of the patella are described. These findings include a typical bone bruise pattern involving the anterolateral aspect of the lateral femoral condyle and inferomedial patella, hemarthrosis, and injury to the medial soft-tissue restraints (especially the medial patellofemoral ligament). After transient dislocation of the patella, patients with significant osteochondral injury or disruption of the medial soft-tissue restraints may benefit from surgical repair. The role of MRI in preoperative planning is discussed as it relates to the detection of osteochondral injuries as well as injury to the medial soft-tissue restraints.